4.5 Article

Aerobic Exercise Training-Induced Changes on DNA Methylation in Mild Cognitively Impaired Elderly African Americans: Gene, Exercise, and Memory Study-GEMS-I

期刊

出版社

FRONTIERS MEDIA SA
DOI: 10.3389/fnmol.2021.752403

关键词

African Americans; Alzheimer's disease; CPG Islands; DNA methylation; mild cognitive impairment; VO(2)max

资金

  1. National Institute on Aging at the National Institutes of Health (NIH) [R01 5R01AG31517, 5R01AG045058]
  2. National Center for Advancing Translational Sciences/NIH through the Clinical and Translational Science Award Program (CTSA) [UL1TR000101]

向作者/读者索取更多资源

This study investigates the effects of aerobic exercise on DNA methylation in older African American individuals with mild cognitive impairment. The results show that aerobic exercise training is associated with changes in global methylation levels and identifies specific genes related to amyloid biology, protein trafficking, and lipoprotein regulation that are affected by exercise-induced methylation changes.
BackgroundDNA methylation at CpG sites is a vital epigenetic modification of the human genome affecting gene expression, and potentially, health outcomes. However, evidence is just budding on the effects of aerobic exercise-induced adaptation on DNA methylation in older mild cognitively impaired (MCI) elderly African American (AAs). Therefore, we examined the effects of a 6-month aerobic exercise-intervention on genome-wide DNA methylation in elderly AA MCI volunteers. DesignElderly AA volunteers confirmed MCI assigned into a 6-month program of aerobic exercise (eleven participants) underwent a 40-min supervised-training 3-times/week and controls (eight participants) performed stretch training. Participants had maximal oxygen consumption (VO(2)max) test and Genome-wide methylation levels at CpG sites using the Infinium HumanMethylation450 BeadChip assay at baseline and after a 6-month exercise program. We computed false discovery rates (FDR) using Sidak to account for multiplicity of tests and performed quantitative real-time polymerase chain-reaction (qRT-PCR) to confirm the effects of DNA methylations on expression levels of the top 5 genes among the aerobic participants. CpG sites identified from aerobic-exercise participants were similarly analyzed by the stretch group to quantify the effects of exercise-induced methylation changes among the group of stretch participants. ResultsEleven MCI participants (aerobic: 73% females; mean age 72.3 +/- 6.6 years) and eight MCI participants (stretch: 75% female; mean age 70.6 +/- 6.7 years) completed the training. Aerobic exercise-training was associated with increases in VO(2)max and with global hypo- and hypermethylation changes. The most notable finding was CpG hypomethylation within the body of the VPS52 gene (P = 5.4 x 10(-26)), a Golgi-associated protein, involved in intracellular protein trafficking including amyloid precursor protein. qRT-PCR confirmed a nearly twofold increased expression of VPS52. Other top findings with FDR q-value < 10(-5), include hypomethylations of SCARB1 (8.8 x 10(-25)), ARTN (6.1 x 10(-25)), NR1H2 (2.1 x 10(-18)) and PPP2R5D (9.8 x 10(-18)). ConclusionWe conclude that genome-wide DNA methylation patterns is associated with exercise training-induced methylation changes. Identification of methylation changes around genes previously shown to interact with amyloid biology, intracellular protein trafficking, and lipoprotein regulations provide further support to the likely protective effect of exercise in MCI. Future studies in larger samples are needed to confirm our findings.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.5
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据